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policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document
was developed. Since that time, new technology may have emerged or new medical literature may
have been published. This Medical Policy will be reviewed regularly and be updated as scientific
and medical literature becomes available.

Description:

Autologous islet cell transplantation performed in conjunction with pancreatectomy, is proposed to reduce the likelihood of insulin-dependent diabetes. Allogeneic islet cell transplantation is being investigated as a treatment or cure for patients with type 1 diabetes.

The islet cells come from the patient (autologous transplant) or from a cadaveric donor (allogeneic transplant). Islet cell transplantation may benefit an individual who is without a functioning pancreas. Currently, only individuals with either chronic pancreatitis or type 1 diabetes mellitus have been subject to clinical investigations.

Chronic Pancreatitis

Chronic pancreatitis is inflammation of the pancreas that does not heal or improve, it gets worse over time and leads to permanent damage. Chronic pancreatitis eventually impairs an individual’s ability to digest food and make pancreatic hormones. Individuals with chronic pancreatitis can experience intractable pain that can only be relieved with a total or near total pancreatectomy. However, the pain relief must be balanced against the certainty that the individual will be rendered an insulin-dependent diabetic.

Autologous islet cell transplantation has been investigated as a technique to prevent this serious morbidity of surgically induced diabetes due to the removal of the individual’s pancreas. The transplant is generally performed during the pancreatectomy procedure, and the islet cells are isolated from the resected pancreas using enzymes, and a suspension of the cells is injected into the portal vein of the patient’s liver. Once implanted, the beta cells in these islets begin to make and release insulin. Because the body recognizes these islet cells as its own, there is no rejection of these cells by the patient’s body.

Although the published literature regarding autologous islet cell transplant is limited, the procedure appears to significantly decrease the occurrence of surgically induced diabetes after total or near total pancreatectomy in patients with chronic pancreatitis. Also, this procedure is not associated with serious complications itself and is performed in patients who are already undergoing a pancreatectomy procedure. Autologous islet cell transplantation may be considered medically necessary and a adjunct to a total or near total pancreatectomy in patients with chronic pancreatitis. The evidence is insufficient to demonstrate the efficacy of autologous islet cell transplantation performed for any other indication.

Type 1 Diabetes Mellitus

Type 1 diabetes is a chronic illness characterized by the body’s inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas. Islet cell autoantibodies (ICAs) are theorized to cause the individual to reject their own islet cells, leading to insulin deficiency. Individuals with type 1 diabetes do not have viable beta cells and therefore, cannot receive an autologous islet cell transplant.

Allogeneic islet cell transplant has been proposed as a treatment for patients with type 1 diabetes to restore normoglycemia (normal glucose levels) and ultimately to reduce or eliminate the long-term complications of diabetes such as retinopathy, neuropathy, nephropathy, and cardiovascular disease. Islet cell transplantation potentially offers an alternative to whole-organ pancreas transplantation. Therefore, islet transplantation has generally been reserved for patients with frequent and severe metabolic complications who have consistently failed to achieve control with insulin-based management.

Allogeneic islet cell transplant is a procedure in which islets are obtained from deceased organ donor and are purified, processed and transferred into the transplant patient. A limitation of allogeneic islet cell transplantation is that 2 or more donor organs are usually required for successful transplantation. A pancreas that is rejected for whole-organ transplant is typically used for islet transplantation. Transplant patients typically receive two infusions with an average of 400,000 to 500,000 islets per infusion. Once implanted in the liver, the beta cells in these islets begin to make and release insulin. The patient will be started on immuosuppressive therapy to prevent allograft rejection.

The techniques for allogeneic islet cell transplants are evolving, and the impact on the net health outcome for patients with type 1 diabetes, not otherwise undergoing surgery, is still uncertain. Longer follow up with larger numbers of patients is needed before conclusions can be drawn about the long-term safety of allogeneic islet cell transplantation and its impact on diabetes mellitus. and associated complications. Therefore, allogeneic islet cell transplantation is considered investigational for all indications.

Practice Guidelines and Position Statements

American Diabetes Association

In 2004, the American Diabetes Association issued a position statement on pancreas transplantation in patients with type 1 diabetes which included the following recommendation: Pancreatic islet cell transplants hold significant potential advantagese over whole gland transplants. However, at this time, islet cell transplantation is an experimental procedure, also requiring systemic immunosuppression, and should be performed only within the setting of controlled research studies.

National Institute for Health and Clinical Excellence (NICE)

In 2008 the National Institute for Health and Clinical Excellence issued guidance on allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus which states: The evidence on allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus shows short-term efficacy with some evidence of long-term efficacy. The evidence on safety shows that serious complications may occur as a result of this procedure. The long-term immunosuppression required is also associated with a risk of adverse events.

During consent, clinicians should ensure that patients understand the potential complications of the procedure and uncertainty about is efficacy in the long term.

Further audit and research should address the effect ot the procedure on quality of life and its long term efficacy, particularly in relation to the complications of diabetes.

In 2008 the National Institute for Health and Clinical Excellence issued guidance on autologous pancreatic islet cell transplantation for improved glycemic control after pancreatectomy which states: The current evidence on autologous pancreatic islet cell transplantation for improved glycemic control after pancreatectomy shows some short term efficacy, although most patients require insulin therapy in the long term. The reported complications result mainly from the major surgery involved in the pancreatectomy (rather than from the islet cell transplantation).

During consent, clinicians should ensure that patients understand that they may require insulin therapy in the long term.

American Society of Transplantation

In 2013 the American Society of Transplantation issued a 3rd edition guideline on the transplantation infectious diseases that includes criteria for transplantation for HIV infected individuals. The criteria for transplantation for HIV infected individuals for kidney/pancreas transplants includes the following:

Meet center specific inclusion criteria

CDC count >200 cells/uL during 3 months before transplantation

Undetectable HIV viral load while receiving antiretroviral therapy

Documented compliance with a stable antiretroviral regimen

Absence of active opportunistic infection and malignancy

Absence of chronic wasting or severe malnutrition

History of hepatitis B or C with lack of evidence of advanced fibrosis or cirrhosis

Acceptance of life-long pneumocystis prophylaxis

Donor free of hepatitis C

Appropriate follow up with providers experienced in the management of HIV

Organ Procurement and Transplantation Network (OPTN)

Islet Registration Status Effective October 2016

A transplant hospital may register an islet candidate on the waiting list with an active status if the candidate meets either of the following requirements:

Is insulin dependent

Has a hemoglobin A1c (HcA1c) value greater than 6.5%

An islet candidate that does not meet either of these requirements must have an inactive status on the waiting list. If the transplant hospital changes a candidate’s status from inactive to active, the transplant hospital must document that the candidate met one of the above requirements.

If the candidate is active and is insulin dependent, then the transplant hospital must document in the candidate’s medical record that the candidate’s insulin status and HbA1c value. The transplant hospital must use the most recent HbA1c test performed within the last six months when determining whether the candidate meets criteria for active status.

Regulatory Status

Islet cells are subject to regulation by the U.S. Food and Drug Administration (FDA), which classifies allogeneic islet cells transplantation as somatic cell therapy requiring pre-market approval. Islet cells also meet the definition of a drug under the Federal Food, Drug and Cosmetic Act. Clinical studies to determine safety and effectiveness outcomes of allogeneic islet transplantation must be conducted under FDA investigational new drug regulation. At least 35 investigational new drug applications have been submitted to the FDA, no center has submitted a biologics license application.

Autologous Pancreas Islet Cell Transplantation

Autologous pancreas islet cell transplantation may be considered medically necessary as an adjunct to a total or near-total pancreatectomy in patients with chronic pancreatitis.

Autologous pancreas islet cell transplantation is considered investigational when the above criteria is not met and for all other indications because the safety and/or effectiveness of this procedure for all other indications can not be established based on available peer reviewed literature.

Allogeneic Pancreas Islet Cell Transplantation

Allogeneic pancreas islet cell transplantation is considered investigational for all indications including the treatment of type 1 diabetes.

The techniques for allogeneic islet cell transplants are evolving; the impact on net health outcomes is still uncertain. Longer follow up with larger numbers of patients is needed before conclusions can be drawn about the safety of allogeneic islet transplantation and its impact on complications of diabetes mellitus, thus the procedure is considered investigational.

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of technology assessment of new and emerging treatments, devices,
drugs, etc.They are developed to
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and therefore are subject to change without notice.